How to use acylcarnitine profiles to help diagnose inborn errors of metabolism

Abstract

Inborn errors of metabolism are a heterogeneous group of conditions which frequently cause diagnostic diffi culties due to their wide range of presenting features. Because many of these disorders overlap considerably in their presentation, a clinical suspicion of metabolic disease often leads to the taking of a "fi rst line metabolic screen", which will typically include all or a combination of the following:▶ blood for ammonia and lactate measurement ▶ urine for organic acid analysis ± glycosaminoglycans ▶ blood for amino acids ▶ blood for acylcarnitine analysis. This article is intended to aid the non-metabolic specialist in understanding the method and rationale for measuring acylcarnitines when investigating children with suspected inborn errors of metabolism and help one appreciate what it does, and more importantly does not, tell about a patient. It is not intended to be a substitute for close communication with one's local metabolic laboratory! BIOCHEMICAL BASISCarnitine is a small intracellular molecule, which facilitates the transport of larger molecules,

Disorders associated with abnormal acylcarnitine profile among high risk Egyptian children

“…The confi rmatory tests help to support the diagnostic value of the abnormal metabolic pattern. Hence, the abnormal presence of a single AC is not diagnostic of fatty acid oxidation disorder (FAOD); because an enzyme defi ciency responsible for oxidation of a certain fatty acids group of the same chain length; will show an increase in almost all ACs within this group (3).…”

“…Analysis of ACP is complicated as the concentration of free carnitine and acylcarnitine varies with age where they decrease normally within the fi rst week of life and dramatically increase in older infants making the interpretation of ACP more reliable (3). Another factor is that many metabolic disorders are accompanied by marked decrease in free carnitine with an elevation in many characteristic ACs.…”

“…Also, the same consequences can be produced from chronic treatment with certain drugs (e.g. valproic acid, cisplatin, and cephalosporin) that cause lowering in free carnitine concentration by different mechanisms (3). The ACP is diagnostic for many inborn errors of metabolism (IEM) like:…”

Tandem Mass Spectrometry Newborn Screening for Inborn Errors of Intermediary Metabolism: Abnormal Profile Interpretation

“…Both situations can lead to a carnitine level that is not sufficient to assure conjugation to acyl residues, and must be considered because if an organic acidemia or a fatty acid oxidation deficiency exists, biomarkers will not be present and the possibility of obtaining a false negative NBS result will increase. Santra et al point out the need of repeating the test after a carnitine load of 100mg/kg when free carnitine is low, in order to avoid obtaining an apparently normal AC profile [129]. On the other hand, babies under carnitine therapy can present elevations that are not attributable to IMD [9,94,129].…”

“…Santra et al point out the need of repeating the test after a carnitine load of 100mg/kg when free carnitine is low, in order to avoid obtaining an apparently normal AC profile [129]. On the other hand, babies under carnitine therapy can present elevations that are not attributable to IMD [9,94,129].…”